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The gut-immune-liver axis in patients with alcohol use disorder and clinically low serum zinc levels.
Thakurdesai, Aishwarya; Jha, Suman K; Erinkitola, Iyabo; Said, Aula; Joshi, Thwisha; Schwandt, Melanie L; Parajuli, Dipendra; Singal, Ashwani K; Kong, Maiying; Cave, Matthew C; Vatsalya, Vatsalya.
Afiliación
  • Thakurdesai A; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Clinical Laboratory for the Intervention Development of AUD and Organ-Severity, University of Louisville, Louisville, Kentucky, USA.
  • Jha SK; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Clinical Laboratory for the Intervention Development of AUD and Organ-Severity, University of Louisville, Louisville, Kentucky, USA.
  • Erinkitola I; Clinical Laboratory for the Intervention Development of AUD and Organ-Severity, University of Louisville, Louisville, Kentucky, USA.
  • Said A; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Clinical Laboratory for the Intervention Development of AUD and Organ-Severity, University of Louisville, Louisville, Kentucky, USA.
  • Joshi T; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Clinical Laboratory for the Intervention Development of AUD and Organ-Severity, University of Louisville, Louisville, Kentucky, USA.
  • Schwandt ML; National Institute on Alcohol Abuse and Alcoholism, NIAAA, NIH, Bethesda, Maryland, USA.
  • Parajuli D; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville, Louisville, Kentucky, USA.
  • Singal AK; Robley Rex VA Medical Center, Louisville, Kentucky, USA.
  • Kong M; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville, Louisville, Kentucky, USA.
  • Cave MC; VA Medical Center, Sioux Falls, South Dakota, USA.
  • Vatsalya V; Department of Bioinformatics and Biostatistics, School of Public Health, University of Louisville, Louisville, Kentucky, USA.
Alcohol Clin Exp Res (Hoboken) ; 2024 Aug 02.
Article en En | MEDLINE | ID: mdl-39095327
ABSTRACT

BACKGROUND:

Alcohol use disorder (AUD) with chronic and heavy alcohol consumption causes alcohol-associated liver disease (ALD). Early-stage ALD exhibits dyshomeostasis of zinc. We investigated the role of zinc deficiency in gut-barrier dysfunction, proinflammatory response, hepatocyte injury, and death, as well as potential sex differences in AUD patients.

METHODS:

Thirty-nine male and female AUD patients were grouped by normal [≥71 µg/dL (Group 1, number (n) = 26)] and low [<71 µg/dL (Group 2, n = 13)] serum zinc levels. Demographics, alcohol intake markers [Lifetime Drinking History (LTDH), heavy drinking days in the past 90-days (HDD90), total drinks in the past 90-days (TD90), number of drinking days in the past 90-days (NDD90), average drinks per day in the past 90 days (AvgDPD90)] were collected. Blood samples were tested for complete blood count (CBC), comprehensive metabolic panel (CMP), coagulation markers, gut-barrier dysfunction markers, cytokines, and hepatocyte death markers.

RESULTS:

Group 2 females exhibited lower LTDH than Group 2 males (p = 0.028), but higher recent drinking. Aspartate transaminase alanine transaminase (ASTALT) ratio was higher (p = 0.049) in Group 2 males compared to Group 1 males. Overall, Group 2 showed threefold higher interleukin 8 (IL-8) levels than Group 1 (p = 0.92); these were sevenfold higher in Group 2 females than Group 1 females. Group 2 females also had higher K18M65, but lower K18M30 than Group 1 females. Necrotic type of cell death (K18M65) was well-described only in Group 2 by the arrangement of lipopolysaccharide (LPS), soluble cluster of differentiation 14 (sCD14), and tumor necrosis factor alpha (TNF-α) (R2 = 0.633, p = 0.037).

CONCLUSION:

Our findings demonstrated the role of the gut-immune-liver axis in describing hepatocyte injury and death in zinc-deficient AUD patients. These patients represented an arrangement of gut-barrier dysfunction and an exacerbated immune response. Shift in the cell-death mechanism from apoptosis in zinc-replete females to necrosis in zinc-deficient females suggests a subclinical to clinical transition of ALD associated with zinc status.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Alcohol Clin Exp Res (Hoboken) Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Alcohol Clin Exp Res (Hoboken) Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos